ZAP70 and Autoimmunity: Indeed, W360P in the kinase domain and W163C mutation in the C-SH2 domain of Zap70 weakens its auto-inhibition resulting in open conformation and significantly lower protein expression and autoimmune disorders by different mechanism; W360P mutation results in hyperactive Zap70, whereas W163C mutated Zap70 is hypoactive due to its inability to bind to phospho-CD3 chains and subsequent lack of Lck-induced phosphorylation (65, 67, 69).